In order to study the relationship between structure and antihyperlipidemic activity the N-alkyl and N-butan-3-one analogs of saccharin, indane-1,3-dione, 3-imino-1-oxoisoindoline, phthalimidine, sultam, indane-1-one, hydroxyphthalimidine, indazolone, homophthalimide, phthalazine-1,4-dione, 1, 8-naphthalimide, glutarimide, succinimide, and maleimide will be synthesized. The ability to lower serum cholesterol and serum triglyceride levels in Sprague Dawley male rats after oral administration in normal and hyperlipidemic states will be determined. Acute toxicity studies (LD50 values) will be determined for potent antihyperlipidemic analogues of this series. Both in vitro and in vivo studies will be carried out to determine if phthalimide analogues suppress the regulatory enzymes of cholesterol synthesis (HMG-CoA reductase), fatty acid synthesis (acetyl CoA carboxylase), and triglyceride synthesis (sn-glycerol-3-phosphate acyl transferase and phosphatidate phosphorylase). The effects of phthalimide analogues on the availability of acetyl CoA for lipogenesis will be assessed by determining ATP-citrate lyase, acetyl CoA synthetase, mitochondrial citrate transport, and cytosol pyruvate level, as well as plasma lipoprotein lipase and adipose lipase activities.